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Delta Omega

2006 Poster Competition Winners

OVERALL- Xiaoyan Song: Association of Serum Ferritin and Mortality in Incident Hemodialysis Patients

Summary:

Background: Each year, about 300,000 patients in U.S. receive hemodialysis (HD) to treat end stage renal disease. Given that almost every HD patient suffers from anemia and thus requires recombinant human erythropoietin (EPO) treatment, intravenous (IV) iron therapy has become one of the most important adjunctive treatments in anemic HD patients. Although IV iron is effective in correcting anemia, excessive iron in human body increases patient's risk of developing infections and cardiovascular diseases. Epidemiological studies addressing iron and mortality in HD patients provided controversial evidences, partially because these studies only followed patients for less than 2 years which were insufficient to assess the causal effect of iron on mortality.

Objective: To examine the relationship between serum ferritin (SF), a marker of body iron storage, and all-cause mortality in incident HD patients.

Method: A prospective longitudinal cohort study. Eligible patients were incident HD patients who were enrolled in the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) study, an ongoing prospective study that had followed 1,041 incident dialysis patients recruited from 81 clinics nationwide since 1995, and had baseline SF values that were measured within 3 months of dialysis onset. Baseline patient characteristics (age, gender, race, smoking, employment and marital status) and co-morbidity were collected through a self-administered questionnaire. Clinical laboratory values including SF were obtained from an electronic database. Death was prospectively identified from medical records, national Death Certificate Index database, and U.S. Renal Disease System. Statistical analyses included descriptive analysis to examine associations between SF (grouped into <100 mg/dL, 100~500 mg/dL, 500~800 mg/dL, and >800 mg/dL for the ease of clinical interpretation), death and covariates. Unadjusted and adjusted Cox regression model was used to determine the independent effect of SF on mortality. Laboratory values including inflammatory marker C-reactive protein (CRP) were adjusted as time-dependent covariates. To further illustrate a potential causal effect of iron on mortality, we analyzed a group of patients who survived for at least 6 months from dialysis onset and excluded SF values that were measured within 6 months before the events (death or censoring) occurred.

Results: Of 767 HD patients enrolled in the CHOICE study, 687 (89.6%) had baseline SF available and 614 (80.1%) survived for at least 6 months after dialysis onset. Patients in the four SF groups were similar in baseline age, race, smoking, marital and employment status, and education levels. Baseline SF was positively associated with CRP (p=0.04), but negatively associated with albumin (p<0.001). No statistical association was found between baseline SF and mortality in the analysis using either whole- or sub- group data. Cox regression model using whole-cohort data found no association between follow-up SF and mortality. Comparing to the reference group 100~500 mg/dL, Hazard Ratio (HR) was 0.74 (95% Confidence Interval (CI): 0.45~1.23), 1.02 (95% CI: 0.75~1.39), and 1.16 (95%CI: 0.93~1.45) for SF<100, 500~800, and >800 mg/dL groups, respectively. Cox regression using sub-cohort data and excluding SF measured in the last 6 months before events occurred revealed that SF <100 mg/dL was associated with elevated mortality (HR: 1.26, 95%CI: 1.01~1.57). The association remained statistically significant after adjusting for CRP and albumin.

Conclusion: We found that low, rather than high, SF was associated with increased mortality. Our results suggested a reverse causal effect when using SF as a marker of body iron to assess its relationship with mortality in HD patients. Further study was warranted to confirm this finding.

Laboratory Research

1st Place- Caren Chancey: Combination of antibodies to CD18 and ICAM-1 reduces transmission of cell-associated HIV-1

Summary:

Background: A better understanding of the interactions between HIV-1 positive cells and the cervical epithelium is essential for development of microbicides to prevent sexual transmission of HIV-1 to women. Our lab has previously demonstrated that cell-associated transmission of HIV-1 by monocytes is the most efficient route of transmission across a model cervical epithelial monolayer and in a hu-PBL-SCID model of vaginal HIV-1 transmission. In addition, antibody to ICAM-1 has been shown to block transmission of cell-associated HIV-1 in both of these models. Use of lactobacilli to produce antibody-like single-chain Fvs (scFv) offers many advantages over traditional microbicides, but the available concentration of antibody is limited by the amount of scFv that can be secreted in vivo. In order to determine whether a significant reduction in the amount of antibody required to block HIV-1 transmission could be achieved, we evaluated the blocking capabilities of antibodies to CD18, the -chain of the ICAM-1 ligands LFA-1 and Mac-1, both separately and in combination with anti-ICAM-1.

Methods: Peripheral blood mononuclear cells (PBMC) infected with HIV-1 BaL were added to the apical side of confluent monolayers of HT-3 cervical epithelial cells grown on permeable transwell supports. After 24 hours, PBMC in the basal compartment were counted, and HIV transmission was measured by p24 ELISA on the basal supernatant. Data were analyzed using one-way ANOVA with Bonferroni correction by the STATA statistical package.

Results: Two different anti-CD18 antibodies, H52 and 7E4, were able to reduce transmission of cell-associated HIV-1 by 90.1% and 67.6%, respectively. Anti-CD18 and anti-ICAM-1 used in 50:50 combination at a total concentration of 5 ug/ml reduced migration of PBMC from HIV-1 infected cultures significantly better (p<0.05) than 20 ug/ml total of either antibody alone.

Conclusions: These findings indicate that a combination of antibodies to the adhesion receptor pair ICAM-1 and CD18 offers better protection against cell-associated HIV-1 transmission than either antibody alone, and that this combination can protect at a concentration which is feasible for use in a lactobacillus-based microbicide delivery system.


2nd- Place- John Pisciotta: Hemozoin Formation and Detection in P. falciparum

Summary:
The intraerythrocytic malaria parasite forms intracellular heme crystals, called hemozoin, as a means of detoxifying free heme released through hemoglobin catabolism. This process is targeted by the quinoline antimalarials. The intracellular mechanism of heme crystallization initiation has not been fully substantiated; however, histidine rich proteins, polar lipid and/or neutral lipids have all been purported to play a role. The current study employs the lipid fixative malachite green to observe neutral lipid nanospheres enveloping nascent hemozoin within P. falciparum digestive vacuoles (DV). Mass spectrometry lipidomics identifies significant saturated mono- and diacylglycerol neutral lipids and a paucity of residual polar lipids associated with purified hemozoin. Under conditions consistent with the DV, the neutral lipid mixture rapidly initiates heme crystallization with reversible, pH dependent quinoline inhibition. Formation of a heme-drug complex is required for drug entry into neutral lipid nanospheres and inhibition of heme crystallization. This work identifies neutral lipid nanospheres as both the microenvironment of heme crystallization and the nonaqueous, nonpolar site of quinoline inhibition.

3rd Place- Judith Easterbrook: Potential Mechanisms Mediating Persistence of Seoul Virus in Male Norway Rats

Summary:
Hantaviruses cause severe disease in humans and pathology is hypothesized to be mediated by sustained, elevated levels of proinflammatory cytokines. Rodents are the natural hosts for hantaviruses; unlike humans, rodents display no pathology during infection, yet remain persistently infected. This study examined whether Seoul virus suppresses rodent host immune responses that would allow persistent infection. Male rats were inoculated with Seoul virus and proinflammatory (interleukin (IL)-1, IL-6, and TNF) and anti-inflammatory (IL-10, IL-1 receptor antagonist (ra), and corticosterone) responses were assessed. Copies of Seoul virus were significantly elevated in the lung 15 and 30 days post inoculation (p.i.). Expression of splenic IL-1 was cyclical, with transcription elevated 3 and 60 days p.i., but reduced to baseline 15-30 days p.i. Interleukin-1 protein production was significantly below baseline 15-60 days p.i. Similar, but less dramatic, trends were observed for transcription of IL-6 and TNF. Expression of IL-10 and IL-1ra remained at baseline 3-30 days p.i., but was significantly elevated 60 days p.i. Synthesis of IL-10, however, was significantly suppressed 3-60 days p.i. Corticosterone concentrations remained low 3-30 days p.i., but were elevated at 60 days p.i. These data indicate that Seoul virus infection suppresses proinflammatory cytokine production. The reduction of proinflammatory immune responses does not correlate with elevation of anti-inflammatory factors produced by the host, including IL-10, IL-1ra, and corticosterone, suggesting that virus-induced immunosuppression may be involved.

Applied Research

1st Place- Xiaoyan Song: Association of Serum Ferritin and Mortality in Incident Hemodialysis Patients

Summary:

Background: Each year, about 300,000 patients in U.S. receive hemodialysis (HD) to treat end stage renal disease. Given that almost every HD patient suffers from anemia and thus requires recombinant human erythropoietin (EPO) treatment, intravenous (IV) iron therapy has become one of the most important adjunctive treatments in anemic HD patients. Although IV iron is effective in correcting anemia, excessive iron in human body increases patient's risk of developing infections and cardiovascular diseases. Epidemiological studies addressing iron and mortality in HD patients provided controversial evidences, partially because these studies only followed patients for less than 2 years which were insufficient to assess the causal effect of iron on mortality.

Objective: To examine the relationship between serum ferritin (SF), a marker of body iron storage, and all-cause mortality in incident HD patients.

Method: A prospective longitudinal cohort study. Eligible patients were incident HD patients who were enrolled in the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) study, an ongoing prospective study that had followed 1,041 incident dialysis patients recruited from 81 clinics nationwide since 1995, and had baseline SF values that were measured within 3 months of dialysis onset. Baseline patient characteristics (age, gender, race, smoking, employment and marital status) and co-morbidity were collected through a self-administered questionnaire. Clinical laboratory values including SF were obtained from an electronic database. Death was prospectively identified from medical records, national Death Certificate Index database, and U.S. Renal Disease System. Statistical analyses included descriptive analysis to examine associations between SF (grouped into <100 mg/dL, 100~500 mg/dL, 500~800 mg/dL, and >800 mg/dL for the ease of clinical interpretation), death and covariates. Unadjusted and adjusted Cox regression model was used to determine the independent effect of SF on mortality. Laboratory values including inflammatory marker C-reactive protein (CRP) were adjusted as time-dependent covariates. To further illustrate a potential causal effect of iron on mortality, we analyzed a group of patients who survived for at least 6 months from dialysis onset and excluded SF values that were measured within 6 months before the events (death or censoring) occurred.

Results: Of 767 HD patients enrolled in the CHOICE study, 687 (89.6%) had baseline SF available and 614 (80.1%) survived for at least 6 months after dialysis onset. Patients in the four SF groups were similar in baseline age, race, smoking, marital and employment status, and education levels. Baseline SF was positively associated with CRP (p=0.04), but negatively associated with albumin (p<0.001). No statistical association was found between baseline SF and mortality in the analysis using either whole- or sub- group data. Cox regression model using whole-cohort data found no association between follow-up SF and mortality. Comparing to the reference group 100~500 mg/dL, Hazard Ratio (HR) was 0.74 (95% Confidence Interval (CI): 0.45~1.23), 1.02 (95% CI: 0.75~1.39), and 1.16 (95%CI: 0.93~1.45) for SF<100, 500~800, and >800 mg/dL groups, respectively. Cox regression using sub-cohort data and excluding SF measured in the last 6 months before events occurred revealed that SF <100 mg/dL was associated with elevated mortality (HR: 1.26, 95%CI: 1.01~1.57). The association remained statistically significant after adjusting for CRP and albumin.

Conclusion: We found that low, rather than high, SF was associated with increased mortality. Our results suggested a reverse causal effect when using SF as a marker of body iron to assess its relationship with mortality in HD patients. Further study was warranted to confirm this finding.

2nd Place- Joachim Bleys: Vitamin / Mineral Supplementation And The Progression Of Atherosclerosis. A Meta-Analysis Of Randomized Controlled Trials

Summary:
Joachim Bleys, MD, MPH; Edgar R. Miller III, MD, PhD; Roberto Pastor-Barriuso, PhD; Lawrence J. Appel, MD, MPH; Eliseo Guallar, MD, DrPH
From the Departments of Epidemiology and Medicine, and the Welch Center for Prevention, Epidemiology and Clinical Research, the Johns Hopkins Medical Institutions, Baltimore, MD (J.B., L.J.A., and E.G.), the National Institute on Aging / National Institutes of Health, Baltimore, MD (E.R.M.), and the Division of Biostatistics, National Center for Epidemiology, Instituto de Salud Carlos III, Madrid, Spain (RPB).

Abstract:
Background: Laboratory and observational studies suggested that antioxidant and B-vitamin supplementation may prevent atherosclerosis. Although trials have not shown a benefit of these supplements on clinical cardiovascular events, it is unknown whether they affect the progression of atherosclerosis as measured by imaging techniques.

Methods and results: We performed a meta-analysis of randomized controlled trials assessing the effect of vitamin / mineral supplementation on atherosclerosis progression. We searched MEDLINE, EMBASE, and CENTRAL for relevant studies. No language restrictions were applied. We separately analyzed trials using antioxidant compounds (vitamins E, C, beta-carotene or selenium) from trials using B-vitamins (folate, vitamin B6 or vitamin B12). The progression of atherosclerosis was evaluated by B-mode ultrasound, intravascular ultrasound, or angiography. Effect sizes were calculated for the difference in slope of atherosclerosis progression between participants assigned to supplements and those assigned to the control group. In trials not involving percutaneous transluminal coronary angioplasty (PTCA), the pooled effect size was -0.06 (95% CI, -0.20 to 0.09; 7 trials) for antioxidants, and -0.93 (95% CI, -2.11 to 0.26; 4 trials) for B-vitamins. In post-PTCA trials, the pooled relative risk for restenosis was 0.82 (95% CI, 0.54 to1.26; 3 trials) for antioxidants and 0.84 (95% CI, 0.34 to 2.07; 2 trials) for B-vitamins.

Conclusions: Our meta-analysis showed no evidence for a protective effect of antioxidant vitamin / mineral and B-vitamin supplementation on the progression of atherosclerosis, thus providing a mechanistic explanation for the lack of effect of these supplements on clinical cardiovascular events.

Key words: Meta-analysis, Antioxidants, Folate, Atherosclerosis, Prevention

3rd Place- Jeffrey Willis: Perceived Neonatal Morbidities in Rural Uttar Pradesh, India: Effects of a Community Mobilization and Behavior-Change Communication Intervention

Summary:
Objective: To test the effects of a community mobilization and behavior-change communication (BCC) intervention on perceived neonatal illnesses in rural Uttar Pradesh, India.

Background: Poor neonatal health is a barrier towards improving child survival. One mechanism of improving newborn health in low-resource, high mortality areas such as rural Uttar Pradesh, India, is mobilizing households to engage in community-based essential newborn health practices. Johns Hopkins University and King George Medical University in Lucknow, India, have implemented a community mobilization and BCC intervention that delivers a package of preventive essential newborn care messages to families and communities in rural Uttar Pradesh. It is hypothesized that this intervention will reduce the incidence of newborn illnesses.

Methods: The study was nested in a cluster-randomized trial of the impact of a package of essential newborn care in Shivgarh, a rural block of Uttar Pradesh. The study prospectively enrolled 802 mothers between February and August, 2005, and administered a structured questionnaire to recently delivered women in Hindi at the end of the neonatal period. Multiple logistic regression analysis was used to evaluate the statistical significance of the interventions on perceived neonatal illnesses.

Results: Newborns in the intervention area had significantly lower odds of perceived diarrhea [Adjusted Odds Ratio (OR) 0.66, 95% C.I. 0.46-0.95] and perceived skin-related complications [Adjusted OR 0.62, 95% C.I. 0.42-0.89)] compared to newborns in the comparison area. On average, the day in which the initial newborn illness was recognized was earlier among households in the comparison arm (10.2 8.0 days after birth) than households in the intervention arm (12.3 8.7 days) (p=0.01).

Conclusions: An intervention program focusing on essential preventive newborn health practices significantly reduced the perceived odds of diarrhea and skin-related complications in newborns during the neonatal period. Onset of neonatal illnesses may also have been delayed. Community mobilization and BCC interventions are important tools to reduce neonatal morbidities, although future research should consider using health professionals to more accurately document the changes in neonatal morbidity rates.


Scientific Posters Submitted to the 2006 Delta Omega Competition

  1. J. Morel Symons A case-crossover study of fine particulate matter air pollution and congestive heart failure hospitalization
  2. Konstantinos Tsilidis Association of obesity, insulin resistance, and other features of the metabolic syndrome with colorectal adenoma in Clue II
  3. Fan Li The invalidity in stratification of affected-sib-pairs on covariates with possible genetic determinants: problem and solution strategies
  4. Ani Manichaikul Don't Use the Bootstrap for QTL Mapping
  5. Mia Papas Dietary intake according to fast food restaurant use among adolescents participating in CLUE II
  6. Edwina Yeung Family History of Coronary Heart Disease and the Risk of Incident Type 2 Diabetes
  7. Nagesh Borse Bibliometric Analysis of Unintentional Injuries in Low and Middle Income Countries
  8. Zohra Patel Community Neonatal Death Audits: a participatory process to mobilize and empower the community for collective action
  9. Larissa Jennings Community health workers in Bangladesh: Negotiation and counseling in newborn care preparedness
  10. Jonathan Brown Screening for child and adolescent mental health problems in primary care using child, parent, and teacher informants
  11. Ali Alam Plasma Levels Of B-Type Natriuretic Peptide In Patients With Unstable Angina Pectoris Or Acute Myocardial Infarction: Prognostic Significance And Therapeutic Implications
  12. Caren Chancey Combination of antibodies to CD18 and ICAM-1 reduces transmission of cell-associated HIV-1
  13. Juhee Cho Overweight and Obesity Among Korean Americans: Are they really at low risk?
  14. Ji Wan Park Association between interferon regulatoruy factor 6 (IRF6) and nonsyndromic cleft lip with or without cleft palate (CL/P) in 4 populations
  15. Hossein Bahrami Natural History of Retinitits Pigmentosa; Changes in Visual Acuity, Contrast Sensitivity, and Visual Field
  16. Alexander Balbir Role of Genetics in the Development of Sleep-Disordered Breathing
  17. Ashley Schempf The Contribution of Preterm Birth to the Black-White Infant Mortality Gap, 1990 and 2000
  18. John Pisciotta Hemozoin Formation and Detection in P. falciparum
  19. Jeffrey Willis Perceived Neonatal Morbidities in Rural Uttar Pradesh, India: Effects of a Community Mobilization and Behavior-Change Communication Intervention
  20. Neal Burton In vivo Attenuation of the Parkinsonian Phenotype by Induction of transcription factor Nrf2
  21. Bryan James Education and executive function in the Baltimore Memory Study
  22. Kristin Nicodemus NRG1 gene and the Risk of Schizophrenia: Does it Depend on Statistical Epistasis between NRG1 Protein-Interaction Partners ERBB4, CHRNA7, AKT1, DLG4, CAPON and NOS1?
  23. Joachim Bleys Vitamin / Mineral Supplementation And The Progression Of Atherosclerosis. A Meta-Analysis Of Randomized Controlled Trials
  24. Judy Easterbrook Potential Mechanisms Mediating Persistence of Seoul Virus in Male Norway Rats
  25. Leora Vegosen Seasonal Birth Patterns in Subgroups of Myositis Suggest a Role for Perinatal Environmental Factors in Etiology
  26. Alezandria Turner Designing HOPE: an intervention to address the mental health needs of Baltimore youth
  27. Kimberly Walton The Impact of Screening Brief Intervention & Referral To Treatment (SBIRT) On Emergency Department (ED) Patients Alcohol Use
  28. Caroline Fichtenberg The impact of differential mixing by sexual activity on racial/ethnic STI disparities: A simulation study
  29. Xiaoyan Song Association of Serum Ferritin and Mortality in Incident Hemodialysis Patient
  30. Jaya Jaya Does Methodology Matter Adolescent Reporting of Sexual Behaviors in a Randomized Trial in Urban India
  31. Wen-Chih Cheng Deleting the anti-death gene FIS1 from S. cerevisiae leads to genetic changes and metabolic reprogramming, with similarities to tumorigenesis
  32. Honghong Zhu Secondhand smoke and breast cancer risk: a population-based prospective cohort study
  33. Maroya Spalding Is lipoylation essential? Conditional disruption of lipoylation in P. falciparum
  34. Belinda Johnston Predictors of Condom Use in Adolescent Mothers
  35. Shaun Morris Blastomycosis in Ontario, 1994-2003
  36. Julia Gage Evidence that taking more cervical biopsies improves the sensitivity of colposcopically-guided biopsy